骨质疏松脆性骨折多发于老年患者，由于成骨细胞及破骨细胞偶联失平衡，导致局部骨修复明显延迟。因此，如何加强骨质疏松性骨折愈合是临床棘手且亟需加以研究解决的问题。本课题组先期研究结果表明使用β-TCP填充骨质疏松大鼠骨缺损时，其修复效果和正常大鼠相比缓慢，同时降解速度也不够理想，进而发现使用PTH不仅可以改善未植骨状态下骨缺损的修复而且材料充填区也有较多的新生血管形成，表明骨质疏松状态下使用PTH可以促进骨缺损区血管生成及骨形成。假设PTH作用于内皮细胞的PTHR激活PKA/ERK信号通路并促进内皮细胞分泌CXCL1，再作用于间充质干细胞并通过CXCR2/AKT通路趋化其迁移，从而进一步加强骨修复。为了验证上述假说，本研究将结合基因工程手段从分子、细胞、动物多个层次，系统研究PTH/PTHR/CXCL1信号通路促进骨质疏松骨修复的作用机制，丰富现有骨修复理论并为新材料新药物开发提供基础。

Osteoporotic fragile fractures occur frequently in elderly patients, due to the loss of balance between osteoblast and osteoclast activity resulting in local bone formation apparent delay . Therefore, finding the means to enhance osteoporotic bone healing is a clinically difficult but vital endeavor. Our early results indicate that the use of β-TCP for treatment of metaphyseal bone defect in osteoporotic rats, with its lower bone turnover, demonstrates slower degradation of β-TCP as compared with normal rats. At the same time, however, its repair is not ideal. Our previous findings also showed that PTH hormone can not only improve osteogenesis without the use of bone graft, but also increase angiogenesis in areas with bone defect. Therefore, we propose that PTH can promote angiogenesis through endothelial cell activation, which will subsequently secrete CXCL1, leading to mesenchymal stem cells inward migration through CXCR2/AKT signaling pathway. In order to verify the above hypothesis, the study will explore molecular and cellular mechanisms with both in vitro and in vivo experiments, to illuminate the PTH/PTHR/CXCL1 signaling pathways in promoting osteoporotic bone defect repair.